Clinical meaning
Dementia is a chronic, progressive syndrome characterized by deterioration of cognitive function beyond what is expected from normal aging. Unlike delirium, which develops acutely and is typically reversible, dementia has a gradual onset and is generally irreversible. The most common type is Alzheimer disease (AD), accounting for 60-70% of all dementia cases. In Alzheimer disease, two hallmark pathological changes occur in the brain: extracellular amyloid-beta plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. Amyloid-beta protein, which is normally produced and cleared from the brain, accumulates into insoluble plaques between neurons when the balance between production and clearance is disrupted. These plaques trigger an inflammatory response, activate microglia (the brain's immune cells), and generate oxidative stress that damages surrounding neurons. Simultaneously, tau protein, which normally stabilizes microtubules within neurons to maintain structural integrity and axonal transport, becomes hyperphosphorylated. This hyperphosphorylated tau detaches from microtubules, aggregates into paired helical filaments, and forms neurofibrillary tangles inside neurons. The tangles disrupt intracellular transport, leading to synaptic dysfunction and eventual neuronal death. The disease typically begins in the hippocampus and entorhinal cortex (explaining...